1. Bioresorbable scaffolds - Academic view-
Patrick W. Serruys, MD, PhD
Yoshinobu Onuma, MD
Thorax centre, Rotterdam
the Netherlands
14:15-14:20, Feb 7th 2012

2. I have no real or apparent conflicts of interest to report.
Patrick W. Serruys, MD PhD
I have no real or apparent conflicts of interest to report.

3. + - “Caged” (Stented) Vessel Compensatory Expansive Remodeling of EEMBL
PIT 5Y + IT FA
Late acquired malapposition
Struts
Lumen Reduction -
Lumen Reduction
Metallic Struts
Lumen Reduction by Intrastent Growth of tissue
The atherosclerotic process can be characterized by a balance of lumen reduction along the vertical axis, and compensatory expansive remodeling along the horizontal axis, as described by Glagov and others. Intimal thickening may become pathological, setting the stage for a process that results in a fibrotic atheroma and ultimately a plaque with fibrotic, fibrofatty tissue, dense calcium and necrotic core.
When the plaque burden exceeds 40%, compensatory remodeling is overwhelmed and lumen reduction is inevitable. Once the stenotic lesion becomes flow limiting, revascularization becomes necessary. Today, revascularization means implantation of a stent for most patients, leaving a vessel that is ‘caged’ by a permanent implant.
One possible fate of a stented vessel segment is neointimal tissue growth within the stent, which leads to a reduction in the lumen size.
This neointimal tissue may also become degenerative, developing into an unstable, vulnerable plaque which can rupture.
Late acquired malapposition has also been demonstrated, where the surrounding vessel wall retracts away from the metallic stent (the stent is unable to expand with the vessel wall). These changes can occur in varying degrees, from the wall ballooning away from the struts creating a crenated appearance of the vessel, to a response so intense that the wall ultimately becomes detached from the tethering struts, creating a frank and severe late acquired malapposition.
These changes in the stented segment over time may lead to late or very late thrombosis.
Ruptured intra-stent plaque - -

4.  #1. Neoatherosclerosis in the metallic cage CD68 Th
Nakazawa et al. JACC 0211  Th
CD68
The atherosclerotic process can be characterized by a balance of lumen reduction along the vertical axis, and compensatory expansive remodeling along the horizontal axis, as described by Glagov and others. Intimal thickening may become pathological, setting the stage for a process that results in a fibrotic atheroma and ultimately a plaque with fibrotic, fibrofatty tissue, dense calcium and necrotic core.
When the plaque burden exceeds 40%, compensatory remodeling is overwhelmed and lumen reduction is inevitable. Once the stenotic lesion becomes flow limiting, revascularization becomes necessary. Today, revascularization means implantation of a stent for most patients, leaving a vessel that is ‘caged’ by a permanent implant.
One possible fate of a stented vessel segment is neointimal tissue growth within the stent, which leads to a reduction in the lumen size.
This neointimal tissue may also become degenerative, developing into an unstable, vulnerable plaque which can rupture.
Late acquired malapposition has also been demonstrated, where the surrounding vessel wall retracts away from the metallic stent (the stent is unable to expand with the vessel wall). These changes can occur in varying degrees, from the wall ballooning away from the struts creating a crenated appearance of the vessel, to a response so intense that the wall ultimately becomes detached from the tethering struts, creating a frank and severe late acquired malapposition.
These changes in the stented segment over time may lead to late or very late thrombosis.

5. Disturbed laminar flow
#2. Permanent protruding metallic struts creates abnormal shear stress pattern
Lumen
Proximal
Distal
Arterial
wall
Drug
Metallic DES BL
Flow 1Y
Disturbed laminar flow 5Y
Reattachment
Flow separation
Fig 8
Re <2000
Recirculation
Turbulent flow

6. #3. In the stented segment, vasomotion is disabled and cyclic strain is eliminated with compliance mismatch and shear stress disturbance
Exercise test
Maier W et al. Circulation. 2002;105:

7. Bioresorbable scaffold
#4. Bioresorption is a real phenomenon
Bioresorbable scaffold
NON APPOSED 6M 2Y BL BL
Boundaries of metallic cage are permanent 1Y 5Y 7 7

8. #5. Reappearance of physiological (cyclic) strain after bioresorption (Serruys et al. Lancet 2009)
Assessment of vascular compliance by elastography:
Pre, Post, 6 and 24 months after bioresorbable scaffolding
Post
0.16
(0.10) 6M
0.28
(0.12)
24M
0.31
(0.17)
Pre
0.50
(SD: 0.27)
Proximal edge
Scaffold
Distal edge

9. #6. Restoration of the normal endothelial morphology and function with vasodilatation induced by intracoronary Acetylcholine
Acetylcholine 1M
“weak”
single junction
dense continuous
Junctions
Pre-vasomotion
Ach
Nitro 3Y

10. Mechanical forces on the vessel wall
#7. Impact of physiological cyclic strain and shear stress essential for the vessel wall biology
The translation of mechanical forces into chemical signals by cells is referred to as ‘mechanotransduction’
Cell Type
ECM protein changes with strain
Static
Cyclic
Cardiac
↑Collagen
↑↑Collagen
fibroblasts
↑↓Others
↑↑Others
Cardiomyocytes
↑↑MMPs
Endothelial Cells
↑GAGs and PGs
↓↓Collagen
↑↓GAGs and PGs
Smooth Muscle Cells
↓Collagen
↑↑Elastin
↑↑GAGs and PGs
↓MMPs
↑MMPs 
Shear Stress 
Pressure
Mechanical forces on the vessel wall
Hahn C and Schwartz M. Nat Rev: Molec Cell Biol. 2009;10:53-62.
Normal responses to physiologic pulsatile cyclic strain and shear stress lead to cellular responses that stabilize the vessel
Gupta V and Grande-Allen K. Cardiovasc Res. 2006;72:

11. #8. Late lumen enlargement, plaque reduction and absence of remodeling
Pre-stenting
Post-stenting
6-month
24-month
3.9mm2
7.1mm2
6.9mm2
10.1mm2
deze biodegradeerbare stent kan stabiliseren een inflammatoire plaque. Op de animatie zien we een plaque groeien met het optreden van een dunne cap – met tenslotte het scheuren van de cap met een stolsel. Een biodegredeerbare stent zou dit kunnen voorkomen. Op de Virtuele histologie van de plaque, zien we de necrotic core, de kern van het vernietigd weefsel van de plaque in contact iis met het lumen van het bloedvat.
Post-stenting zien we de appositie van de stent. Na zes maanden zijn de stent struts nog zichtbaar. Na 2 jaar is er een laag van fibrotisch weefsel dat de nectrotic core afdekt.
Vessel (mm2)
13.49*
13.79
12.68
Lumen (mm2)
6.04
5.19
5.46
Plaque (mm2)
7.44*
8.60
7.22
Δ-4%
Δ+11%
Δ-13%
Serruys et al. Lancet 2009 11

12. + - Bioresorbable Scaffold – A new treatment Paradigm
Compensatory Expansive Remodeling of EEM 2Y 6M BL
PIT + IT FA
Lumen Enlargement by Plaque Regression
Struts -
Lumen Reduction
Scaffolding
Lumen Enlargement By Bioresorbable Scaffolding -
Bioresorbable Scaffold – A new treatment Paradigm
for Atherosclerotic Plaque -

13. Insight on evolution of late luminal loss over times
BVS 1.1 and Xience V (non-matched population)
6M BVS(Cohort B): 0.19±0.18 mm (N=42)
6M EES (SPIRIT I): 0.10±0.23 mm (N=22) mm

14. 12 months Insight on evolution of late luminal loss over times
BVS 1.1 and Xience V (non-matched population)
12 months
12M BVS (Cohort B): 0.27 ± 0.25 mm (N=56)
12M EES (SPIRIT I): 0.23 ± 0.29 mm (N=22) mm

15. 24 months Insight on evolution of late luminal loss over times
BVS 1.1 and Xience V (non-matched population)
24 months
24M BVS (Cohort B): 0.27 ± 0.20 mm (N=38)
24M EES (SPIRIT II): 0.33 ± 0.37mm (N=96) mm